Genome-wide association analysis of endometriosis in Indian women supports shared genetic susceptibility and suggestive population specific signals

Abstract

Endometriosis is an estrogen-dependent, chronic gynaecological disorder affecting approximately 10% of women of reproductive age and is associated with pelvic pain, infertility, and reduced quality of life. Genetic studies indicate substantial heritability, yet genome-wide association studies (GWAS) have predominantly focused on European populations, with limited evidence from South Asian groups. We conducted a GWAS in 2523 participants from a nationwide, multicentre endometriosis case–control study in India. Genetic susceptibility in Indian women showed both shared features with other populations and evidence of potential population-specific signals. Twenty-one loci demonstrated suggestive associations ( p < 1 × 10⁻ 5 ). The strongest signal mapped to chromosome 13 within a long non-coding RNA and in regulatory elements upstream of SHISA2 . Colocalization analysis showed shared genetic effects with SHISA2 expression in thyroid tissue and methylation sites in the endometrium. A polygenic risk score derived from European populations demonstrated comparable predictive performance in the Indian cohort. Meta-analysis with a Japanese GWAS replicated two known genome-wide significant associations near WNT4 and CDKN2B-AS1 , supporting shared genetic susceptibility across populations. No variant reached genome-wide significance in the discovery cohort alone. This study highlights the importance of expanding genetic studies to diverse populations to improve generalisable genetic risk estimates, biological understanding and equitable precision medicine in women’s health.